Theurapeutic Honey – Cancer and Wound Healing

Also see:
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Sugar (Sucrose) Restrains the Stress Response
Thumbs Up: Fructose

“Applying glucose and insulin topically to the wound, it heals quickly. The very old practice of treating deep wounds with honey or granulated sugar has been studied in controlled situations, including the treatment of diabetic ulcers, infected deep wounds following heart surgery, and wounds of lepers. The treatment eradicates bacterial infections better than some antiseptics, and accelerates healing without scarring, or with minimal scarring. The sugar regulates the communication between cells, and optimizes the synthesis of collagen and extracellular matrix.” -Ray Peat, PhD

Ostomy Wound Manage. 2009 Jan;55(1):38-47.
Using leptospermum honey to manage wounds impaired by radiotherapy: a case series.
Robson V, Cooper R.
Radiation-induced tissue injury and wounds with radiation-impaired healing are traumatic for patients and challenging for their caregivers. Standardized management approaches do not exist. The effect of Leptospermum honey as a primary dressing for managing these wounds was assessed in four patients (age range 63 to 93 years) who had previously undergone radiotherapy that left them with fragile friable areas of damaged skin that did not respond to conventional treatment. Compromised areas involved the neck, cheek, groin/perineum, and chest. In patients 1 and 2, after topical application of honey via hydrofiber rope and nonadhesive foam, respectively, improvements in the size and condition of wound/periwound area and a reduction in pain were noted before death or loss to follow-up. After including honey in the treatment regimen of patients 3 and 4, complete healing was noted in 2.5 weeks (with honey and paraffin) and 6 weeks (with honey-soaked hydrofiber rope), respectively. No adverse events were reported. Honey as an adjunct to conventional wound/skin care post radiation therapy shows promise for less painful healing in these chronic wounds. Prospective, randomized, controlled clinical studies are needed to confirm these observations.

Invest New Drugs. 2010 Oct;28(5):624-33. Epub 2009 Aug 25.
Involvement of non-protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induced apoptosis.
Jaganathan SK, Mandal M.
Honey is a complex mixture of different biologically active constituents. Honey possesses anti-inflammatory, antioxidant and antitumor properties. Our chief investigation was to assess the honey induced apoptosis and its molecular mechanism in colon cancer cell growth inhibition. Honey exerted antiproliferative potential against the HCT-15 and HT-29 colon cancer cells as assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometric analysis showed the increasing accumulation of hypodiploid nuclei in the sub-G(1) phase of cell cycle indicating apoptosis. Honey transduced the apoptotic signal via initial depletion of intracellular non protein thiols, consequently reducing the mitochondrial membrane potential (MMP) and increasing the reactive oxygen species (ROS) generation. An increasing earlier lipid layer break was observed in the treated cells compared to the control. Honey induced apoptosis was accompanied by up-regulating the p53 and modulating the expression of pro and anti-apoptotic proteins. Further apoptosis induction was substantiated using DNA fragmentation assay and YO-PRO-1 staining. Results showed honey as a plausible candidate for induction of apoptosis through ROS and mitochondria-dependent mechanisms in colon cancer cells. This will promote honey as a potential chemotherapeutic agent against colon cancer.

Phytother Res. 2011 Apr;25(4):619-23. doi: 10.1002/ptr.3293. Epub 2010 Sep 13.
Oral administration of Aloe vera and honey reduces Walker tumour growth by decreasing cell proliferation and increasing apoptosis in tumour tissue.
Tomasin R, Gomes-Marcondes MC.
Cancer is diagnosed in approximately 11 million people and is responsible for almost 8 million deaths worldwide every year. Research in cancer control has shown the importance of co-adjuvant therapies. Aloe vera may reduce tumour mass and metastasis rates, while honey may inhibit tumour growth. This study verified the influence of Aloe vera and honey on tumour growth and in the apoptosis process by assessing tumour size, the cell proliferation rate (Ki67-LI) and Bax/Bcl-2 expression at 7, 14 and 20 days after Walker 256 carcinoma implant in Wistar rats distributed into two groups: the WA group – tumour-bearing rats that received a gavage with a 670 µL/kg dose of Aloe vera and honey solution daily, and the CW group – tumour-bearing rats which received only a 0.9% NaCl solution. The effect of Aloe vera and honey against tumour growth was observed through a decrease in relative weight (%) and Ki67-LI in tumours from the WA group compared with those from the CW group. The Bax/Bcl-2 ratio increased in tumours from the WA group at all tested timepoints. These data suggest Aloe vera and honey can modulate tumour growth by reducing cell proliferation and increasing apoptosis susceptibility.

Vopr Onkol. 1990;36(6):704-9.
The antitumor properties of honey.
Gribel’ NV, Pashinskiĭ VG.
The experimental evaluation of antitumor properties of honey was carried out using five strains of rat and murine tumors. Honey revealed moderate antitumor and pronounced antimetastatic effects. Honey potentiated the antitumor activity of 5-fluorouracil and cyclophosphamide.

J Biomed Biotechnol. 2010;2010:989163. Epub 2010 Mar 28.
Effect of honey and eugenol on Ehrlich ascites and solid carcinoma.
Jaganathan SK, Mondhe D, Wani ZA, Pal HC, Mandal M.
Ehrlich ascites carcinoma is a spontaneous murine mammary adenocarcinoma adapted to ascites form and carried in outbred mice by serial intraperitoneal (i/p) passages. The previous work from our laboratory showed that honey having higher phenolic content was potent in inhibiting colon cancer cell proliferation. In this work, we extended our research to screen the antitumor activity of two selected honey samples and eugenol (one of the phenolic constituents of honey) against murine Ehrlich ascites and solid carcinoma models. Honey containing higher phenolic content was found to significantly inhibit the growth of Ehrlich ascites carcinoma as compared to other samples. When honey containing higher phenolic content was given at 25% (volume/volume) intraperitoneally (i/p), the maximum tumor growth inhibition was found to be 39.98%. However, honey was found to be less potent in inhibiting the growth of Ehrlich solid carcinoma. On the other hand, eugenol at a dose of 100 mg/kg i/p was able to inhibit the growth of Ehrlich ascites by 28.88%. In case of solid carcinoma, eugenol (100 mg/kg; i/p) showed 24.35% tumor growth inhibition. This work will promote the development of honey and eugenol as promising candidates in cancer chemoprevention.

Journal of Biomedicine and Biotechnology Volume 2009 (2009), Article ID 830616, 13 pages doi:10.1155/2009/830616
Antiproliferative Effects of Honey and of Its Polyphenols: A Review
Saravana Kumar Jaganathan and Mahitosh Mandal
Honey has been used since long time both in medical and domestic needs, but only recently the antioxidant property of it came to limelight. The fact that antioxidants have several preventative effects against different diseases, such as cancer, coronary diseases, inflammatory disorders, neurological degeneration, and aging, led to search for food rich in antioxidants. Chemoprevention uses various dietary agents rich in phytochemicals which serve as antioxidants. With increasing demand for antioxidant supply in the food, honey had gained vitality since it is rich in phenolic compounds and other antioxidants like ascorbic acid, amino acids, and proteins. Some simple and polyphenols found in honey, namely, caffeic acid (CA), caffeic acid phenyl esters (CAPE), Chrysin (CR), Galangin (GA), Quercetin (QU), Kaempferol (KP), Acacetin (AC), Pinocembrin (PC), Pinobanksin (PB), and Apigenin (AP), have evolved as promising pharmacological agents in treatment of cancer. In this review, we reviewed the antiproliferative and molecular mechanisms of honey and above-mentioned polyphenols in various cancer cell lines.

WMJ. 2008 Jul;107(4):187-90.
Practical considerations of using topical honey for neuropathic diabetic foot ulcers: a review.
Eddy JJ, Gideonsen MD, Mack GP.
It is increasingly important to identify and use low-cost effective dressings for treating diabetic foot ulcers as medical costs and rates of diabetes continue to rise. Honey is an inexpensive moist dressing with antibacterial and tissue-healing properties that has shown promise in the medical literature. Many clinicians are unfamiliar with its use, but patients with diabetic foot ulcers may wish to try honey therapy or discuss it with their physicians. The purpose of this review is to familiarize physicians with practical aspects of using honey to treat diabetic foot ulcers.
The authors have experience using topical honey and are currently conducting a randomized controlled trial of its effectiveness in treating diabetic foot ulcers. In this review, the authors summarize evidence of honey’s effectiveness, its hypothesized mechanism of action, potential risks and benefits, the types of honey available, and the nature of its application. Critical aspects of ulcer care are also reviewed.
Honey is a low-cost topical therapy with important potential for healing. Its use may be considered in diabetic foot ulcers after a discussion of risks and benefits and in conjunction with standard wound care principles.

Diabetes Res Clin Pract. 2010 Sep;89(3):276-81. Epub 2010 Jun 19.
The clinical and cost effectiveness of bee honey dressing in the treatment of diabetic foot ulcers.
Moghazy AM, Shams ME, Adly OA, Abbas AH, El-Badawy MA, Elsakka DM, Hassan SA, Abdelmohsen WS, Ali OS, Mohamed BA.
Honey is known, since antiquity, as an effective wound dressing. Emergence of resistant strains and the financial burden of modern dressings, have revived honey as cost-effective dressing particularly in developing countries. Its suitability for all stages of wound healing suggests its clinical effectiveness in diabetic foot wound infections. Thirty infected diabetic foot wounds were randomly selected from patients presenting to Surgery Department, Suez Canal University Hospital, Ismailia, Egypt. Honey dressing was applied to wounds for 3 months till healing, grafting or failure of treatment. Changes in grade and stage of wounds, using University of Texas Diabetic Wound Classification, as well as surface area were recorded weekly. Bacterial load was determined before and after honey dressing. Complete healing was significantly achieved in 43.3% of ulcers. Decrease in size and healthy granulation was significantly observed in another 43.3% of patients. Bacterial load of all ulcers was significantly reduced after the first week of honey dressing. Failure of treatment was observed in 6.7% of ulcers. This study proves that commercial clover honey is a clinical and cost-effective dressing for diabetic wound in developing countries. It is omnipresence and concordance with cultural beliefs makes it a typical environmentally based method for treating these conditions.

Journal of ApiProduct & ApiMedical Science Vol. 1 (2) pp. 29 – 36, 10.3896/IBRA. April 2009
Honey Constituents and their apoptotic effect in colon cancer cells
Saravana Kumar Jaganathan, Mahitosh Mandal.
Honey finds a vital role in various applications using its antibacterial and anti-inflammatory properties. Our objective was to study the constituents and explore the apoptotic effect of the selected crude honey samples in colon cancer cell lines namely HCT 15 and HT 29. Phenolic content and various functional groups in the honey were analysed using Folin-Ciocalteau method and Fourier Transformed Infrared Spectrophotometer (FTIR). The phenolic content of the honey varied among the different samples. Phenolic content expressed as Gallic acid equivalent (GAE) ranged from 29.96 ± 1.54 to 65.08 ± 4.56 mg of GAE/ 100 g of honey. FTIR results indicated the honey sample to be a mixture of numerous compounds including carboxylic acids, aldehydes, alkynes and nitrites. We had also investigated the fluorescence compounds present in the honey after excitation set at 250 nm (emission: 280-750 nm), 290 nm (emission: 305-750 nm). Fluorescence spectroscopy depicted the variation of physio-chemical properties of honey according to their origin as observed by the varying intensity of fluorescent compounds present in the samples. The anti-proliferative effect of the samples in colon cancer cells was explored using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. MTT assay revealed the honey sample containing higher phenolic content showed significant anti-proliferative effect against colon cancer cells. Propidium iodide (PI) staining of 3 % honey treated cells indicated a significant number of cells accumulating in Sub-G1 phase (indicator of
apoptosis) after 24 hours. Further, in HT 29 cells, honey elevated the caspase-3 level and displayed typical ladder pattern confirming apoptosis. Most of the drugs used in the cancer are apoptotic inducers, hence apoptotic nature of honey is considered vital.

Am J Surg. 1983 Mar;145(3):374-6.
Acceleration of wound healing by topical application of honey. An animal model.
Bergman A, Yanai J, Weiss J, Bell D, David MP.
Commercial unboiled honey was applied topically to open wounds of 12 mice. Twelve other mice served as a control group and their wounds were dressed with saline solution only. Wound healing was judged histopathologically by measuring the thickness of granulation tissue, epithelization from the periphery of the wound, and the size of the open wounds. The animals were killed 3, 6, and 9 days from the day they were wounded and treated, and their wounds were examined histopathologically. According to the three mentioned criteria, wounds of the honey-treated animals healed much faster than the wounds of the control animals (p less than 0.001). Unboiled commercial honey seems to accelerate wound healing when applied topically due to its energy-producing properties, its hygroscopic effect on the wound, and its bacteriocidic properties. Our results suggest that honey applied topically on open wounds accelerates the healing process.

West Afr J Med. 2004 Apr-Jun;23(2):114-8.
Enhanced wound contraction in fresh wounds dressed with honey in Wistar rats (Rattus Novergicus).
Osuagwu FC, Oladejo OW, Imosemi IO, Aiku A, Ekpos OE, Salami AA, Oyedele OO, Akang EU.
Due to reports that honey accelerates wound healing, an investigation on its role in wound contraction in fresh wounds inflicted on wistar rats was carried out.
Twenty adult male wistar rats had 2cm by 2cm square wound inflicted on their right dorsolateral trunk. They were divided into two groups. The experimental group had their wounds dressed with honey while the control group had normal saline dressing. Wound dressing was done every five days and measurements taken at each dressing. Wound morphology was also assessed.
Dressing with honey significantly enhanced percentage wound contraction on day 10 with value of 79.20+/-2.94 compared to control value of 53.50+/-4.32. p=0.0. The mean wound measurement on day 10 reduced significantly in honey group, 1.15+/-0.18 compared to control group 2.38+/-0.28. p=0.002. However, there was no significant difference in fibroblast count per high power field in honey group 68.0+/-2.59 compared to control 90.2+/-17.40, p=0.242. Honey dressing increased mean blood vessel count per high power field, 18.8+/-3.77 albeit non significantly when compared to control value of 13.4+/-2.44, p=0.264. Also honey dressing caused increased granulation tissue formation in wounds dressed with honey compared to control group.
Our study suggests that honey dressing enhances wound contraction in fresh wounds which is one of the key features of wound healing.

Zentralbl Veterinarmed A. 1998 Apr;45(3):181-8.
Effects of topical application of honey on cutaneous wound healing in rabbits.
Oryan A, Zaker SR.
Although it has been known for many centuries that honey can accelerate wound healing, there have only been isolated reports of its use in the healing of burns, ulcers, infected wounds and open wounds. None of these reports developed a model to assess the changes in morphological and biochemical properties due to topical application of honey on cutaneous wounds. In the present investigation, efficacy of honey in the healing of cutaneous wounds of rabbits was studied on the basis of histopathological and biochemical changes. For this reason 40 healthy White New Zealand rabbits were randomly assigned to four equal groups. Using aseptic surgical technique, a 3 cm incision was made on the skin of the left thigh of each rabbit and the wounds of five rabbits in each group were twice daily treated with topical application of 5 ml pure unheated honey. The other half remained as untreated controls. Rabbits in groups A, B, C and D were biopsied on days 2, 7, 14 and 21 postoperatively respectively, and biopsies from the lesions of all groups were collected for histopathological studies and from groups C and D for biomechanical evaluations as well. Treated lesions showed less oedema, fewer polymorphonuclear and mononuclear cell infiltration, less necrosis, better wound contraction, improved epithelialization and lower glycosaminoglycan and proteoglycan concentration on days 2 and 7 postoperatively and better tissue organization and consequently an improved tissue ultimate strength and yield strength on days 14 and 21 postoperation. These findings suggest that honey applied topically on cutaneous wounds accelerates the healing processes and appears to have an important property that makes it ideal as a dressing for cutaneous wounds.

International Journal of Oral & Maxillofacial Surgery
Volume 39, Issue 12 , Pages 1181-1185, December 2010
Effect of topical honey on limitation of radiation-induced oral mucositis: an intervention study
B. Khanal, M. Baliga, N. Uppal
Radiation therapy for oral carcinoma is therapeutically useful in dose of at least 6000cGy but causes mucositis that severely interferes with oral function. The literature indicates that honey appears to promote wound healing, so the authors investigated whether its anti-inflammatory properties might limit the severity of radiation-induced oral mucositis. A single-blinded, randomized, controlled clinical trial was carried out to compare the mucositis-limiting qualities of honey with lignocaine. A visual assessment scale permitted scoring of degrees of mucositis and statistical evaluation of the results was performed using the χ2 test. Only 1 of 20 patients in the honey group developed intolerable oral mucositis compared with the lignocaine group, indicating that honey is strongly protective (RR=0.067) against the development of mucositis. The proportion of patients with intolerable oral mucositis was lower in the honey group and this was statistically significant (p=0.000). Honey applied topically to the oral mucosa of patients undergoing radiation therapy appears to provide a distinct benefit by limiting the severity of mucositis. Honey is readily available, affordable and well accepted by patients making it useful for improving the quality of life in irradiated patients.

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